1. Field of the Invention
The present invention relates to a composition for use in the oral cavity for the maintenance of healthy teeth and gingival tissue and, more specifically, to a composition for the maintenance of oral health which also stimulates the respiration of gingival tissue and promotes cellular proliferation and growth.
2. Description of the Related Art
It is known that substances, or factors, which stimulate the respiratory function of tissue and promote cellular growth and proliferation are produced when living cellular matter is injured under very specific conditions. The cellular matter can be derived from rat, mouse or chick embryos, rat spleen or liver, various types of bacteria, etc. The most conveniently available source of this matter is live Brewer's yeast (Saccharomyces cerevisiae) which, under the proper process conditions, yields a derivative which is now widely used for the treatment of hemorrhoids. This derivative has been variously designated as Live Yeast Cell Derivative (LYCD), Skin Respiration Factor (SRF), or Tissue Respiration Factor (TRF). It has been shown that TRF contains nucleotides, nucleosides, including guanine and adenine, amino acids, especially alanine, arginine and tyrosine; mono-and disaccharides, and phosphorus containing compounds.
The mechanism of the action of TRF in its enhancement of tissue respiration appears to depend, in part, on the stimulation of the enzyme peroxydase (via the oxidation of pyrogallol to purpurogallin) and catalase (splitting of hydrogen peroxide). These enzymatic processes are involved in the respiratory process, in the cytochrome portion of the respiratory chain.
In addition, investigations by Goodson, et al., infra, have produced evidence that TRF stimulates the oxygen utilization of human fibroblasts. Studies with human skin specimens as well as rat epithelium have shown that TRF caused an increase in the amount of collagen synthesized by the fibroblasts. These findings serve to indicate that the increased oxygen consumption is linked to increased collagen synthesis by the cell.
Numerous articles have been published in the scientific and lay literature and several issued patents support the highly beneficial effects of TRF on wound healing, the treatment of burns and the amelioration of skin disorders. Some of the relevant patents and publications are:
Sperti, G., U.S. Pat. No. 2,239,345 granted Apr. 22, 1941; PA1 Sperti, G., U.S. Pat. No. 2,320,478, granted June 1, 1943; PA1 Sperti, G., U.S. Pat. No. 2,320,479, granted June 1, 1943; PA1 Goldman, H. M. and Cohen, D. W.: Periodontal Therapy, 6th edition; PA1 Goldberg, J. V. et al., Your mouth is your business: The dentist's guide to better health, The C. V. Mosby Co., 1980; PA1 Walker, J. A. and Helling, D. K.: Oral Health Products in Handbook of Nonprescription Drugs, 7th edition, Appleton, Century-Crofts, 1980; PA1 Goodson, W. et al.: J. Surgical Res., 21, 125-129 (1976), "Augmentation of some aspects of wound healing by a "Skin Respiratory Factor" PA1 Kaplan, J. Z.: Acceleration of wound healing by a Live Yeast Cell Derivative, Archives of Surgery, September. 1984, 119, 1005-1008; PA1 Cook, E. S.: Skin health and respiration, Part 1 (January. 1939) Part 2 (August. 1939) Chemical Products, Publisher: Science Service, London, U.K. PA1 Kreke, C. W. and Suter, A.: Activity mechanism of Yeast Extracts in Stimulating Respiration, J. Bio. Chem., 160, No. 1, 105-111 (1945); PA1 Cook, E. S. and Kreke, C. W.: Effects of yeast extracts and phenylmercuric nitrate on yeast respiration and growth, Proc. Soc. Exp. Biol. and Med., 53, 222-225 (1943); and PA1 Subramanyam, K. et al.: Effects of Preparation-H on wound healing in the rectum of man, J. Digest. Dis. and Sci., 129, 9, 829-32 (1984). PA1 M. J. Ostro: Liposomes. Marcel Dekker, Inc. New York, 1983 PA1 G. Gregoriades (ed.): Liposome Technology. CRC Press, 1984 PA1 M. J. Ostro: Liposomes, Scientific American, 256, No. Jan. 1, 1987 PA1 Vanlerberghe et al.: U.S. Pat. No. 4,247,411, Jan. 27, 1981 PA1 Redziniak et al.: U.S. Pat. No. 4,508,703, Apr. 2, 1985 PA1 Handjani et al.: U.S. Pat. No. 4,608,211, Aug. 26, 1986
In addition, the American Home Products Corporation has sponsored a large number of clinical studies which have been submitted to the Food and Drug Administration in support of their hemorrhoidal product Preparation H which includes TRF as the active agent. These studies have become available to the public under the Freedom of Information Act.
In a 1986 patent to Mazarin, U.S. Pat. No. 4,575,457, a pharmaceutical composition which when employed as a dentifrice is said to provide an effective therapy for gingivitis, is disclosed which comprises skin respiratory factor (SRF), and bicarbonate, fluoride and zinc salts. Since zinc salts are well-known and widely-used as astringents, the employment of such salts, and other astringents, would serve to harden the protein present in the gingivae and thus prevent or severely retard the penetration and absorption of the SRF into the gingivae. Furthermore, zinc ions will tend to inactivate SRF by precipitation and denaturation of the SRF polypeptide. Thus, the benefits to be obtained by the use of SRF in the prevention or amelioration of periodontal disease would be entirely or substantially negated by following the teaching of the Mazarin patent. In addition, since zinc salts are usually acidic in nature, they would react with the bicarbonate in Mazarin's composition causing its immediate breakdown and evolution of carbon dioxide. Accordingly, Mazarin's composition is totally lacking in commercial feasibility.